Phosphorus-containing thioureas



United States Patent C 3,083,135 PHGSPHORUS-CONTAINING THIGUREAS GlennR. Price, South Chicago Heights, and Edward N.

Walsh, Chicago Heights, 111., and James T. Hallett, Saratoga, Califi,assignors to Stautfer Chemical Company, New York, N.Y., a corporation ofDelaware No Drawing. Filed June 15, 1962, Ser. No. 202,635

10 Claims. (Cl. 167-42) This invention relates to a new class ofthioureas in which one of the nitrogen atoms of the thiourea group isSubstituted with a phosphoro ester group and the second nitrogen atom issubstituted with at least one hydroxyl alkyl or phenyl-substitutedhydroxyalkyl group, a process for preparing said thioureas, and theirmethod of use as pest controlling agents.

The compounds of the present invention have the general formula whereinR :and R are lower-alkyl, X is selected from the group consisting ofsulfur and oxygen, R is selected from the group consisting ofhydroxyalkyl and phenyl-substituted hydroxyalkyl radicals, and R isselected from the group consisting of hydrogen, lower-alkyl, aryl, and Ras previously defined. Suitable lower-alkyl radicals for R, R and Rinclude methyl, ethyl, propyl, isopropyl, amyl, octyl, and the like. Thehydroxyalkyl and phenyl-substituted hydroxyalkyl radicals of R includesuch members as methanol, ethanol, l-propanol, Z-propanol,2-rnethyll-propanol, 2-ethyl-2-propanol, 2-octanol, Z-hydroxy-Z-phenyl-ethyLl, etc. The aryl radicals represented by R are monocyclicradicals and substituted monocyclic radicals such as phenyl, halo andalkoxy-substituted phenyls. Examples of the aryl radicals include4-chlorophenyl, 2,4- dichlorophenyl, 4-alkoxyphenyl, 4-bromopheny1, and2- chloro-4 methoxyphenyl.

The compounds of the present invention may be pre pared according to thefollowing general reaction:

RIO/ RIO wherein R, R R R and X are as defined hereinbefore. Theproducts of the reaction are viscous oils or solids. Stoichiometricratios of reactants are normally used and yields are generallyquantitative. In the preferred method of reaction, an organic solvent orwater is preferably used to solubilize or disperse the reactants. A mongsuitable organic solvents are acetone, hexane, benzene, ethanol, and thelike. The reaction proceeds rather rapidly at temperatures even as lowas C. or lower, and the prodnot is stable at fairly high temperatures,at least as high as C. Nevertheless, a preferred temperature rangewithin which the highest product yields are obtained is between about 0C. and 50 C.

Although the compounds of the present invention show pesticidal activitygenerally, their miticidal activity, especially with the two-spottedmite, Tetranychus telarius, is unexpectedly high. This is due to thepresence of the hydroxyl group in the thioureau portion of the molecule.The closely related phosphorus-containing thioureas (some of which hasbeen known heretofore) lacking the hydroxyl group have, if any, a lowdegree of pesticidal activity and, almost invariably no activity at allwith regard to mites. To illustrate the foregoing, the thioureacompounds disclosed in German Patent No. 952,712, issued November 22,1956, in which one nitrogen is substituted with a phosphorothio estergroup and the second nitrogen is linked to hydrogen, alkyl, phenyl,alkoxyphenyl, and the like, are found to be virtmally ineffective aspesticides and/ or miticides. The miticidal activity of compounds of thepresent invention is compared with the activity of some closely relatedphosphorus-containing thioureas in Table I wherein the percentage killamong the pest species is reported for a percentage concentration of thecandidate compound in aqueous dispersion. A slanted line is used a tosepanate the percentage kill, shown in the left, from the percentageconcentration shown on the right.

' In testing for miticidal activity, young pinto bean plants in theprimary leaf stage were used as host plants for the mites. Bean plantswere infested with several hun dred mites and then sprayed to run-01fwith an aqueous test dispersion prepared as described hereinafter.Sprayed plants were transferred to a greenhouse and held for fourteendays. Miticidal and ovicidal activity of the test compounds weredetermined after seven and fourteen days.

The following examples illustrate the principles of the invention andinclude the best modes presently known for use in practice of theseprinciples.

N (Cl-1 (CH CHOHCHQ To a solution of 19.5 grams (0.10 mole) of0,0-diethy phosphoroisothiocyanatidate in 159 ml. of acetone was added asolution of 8.9 grams (0. 10 mole) of 2-methylamino propanol-2 in 50 ml.of acetone over athirty minute period at room temperature. The reactionmixture was allowed to stir at room temperature for another hour, thesolvent removed, and the product concentrated to 60 C. at 1.0 min. of Hgpressure to yield 27.5 grams (97%) of N-(0,0-diethylphosphoryl)-N(methyl) N (2hydroxypropyl-l) thiourea analyzing as 10.9% P as comparedto 10.8% P theoretical.

Example 2 To a mixture of 17.8 grams (0.20 mole) of 2-ethylamino ethanolin 59 ml. of hexane was added 42.0 grams (0.20 mole) of0,0-diethylphosphoroisothiocyanato thio nate in 50 ml. of hexane over a50 minute period at 0 C. The reaction product,N-(0,0-diethylphosphorothiono)- N-(ethyl)-N-(5-hydroxyethyl) thiourea,separated as a White solid in near quantitative yield. Recrystallizationfrom a benzenehexane mixture gave the pure product as a white solid, MP.59 C., analyzing as 10.1% P and 21.2% S as compared to 10.2% P and 21.3%S, theoretical.

Example 3 To a solution of 19.5 grams (0.10 mole) of0,0-diethylphosphoroisothiocyanatidate in 159 ml. of acetone was added asolution of 16.5 grams (0.10 mole) of 1- phenyl-Z-ethylamino ethanol in50 ml. of acetone over a 30 minute period at 30 C. The reaction mitxurewas stirred for 30 more minutes at room temperature, the solvent removedby heating to 55 C. and the product concentrated to 60 C. at 1.5 mm. ofHg pressure to yield 36.0 grams (100%) of N-(0,0-diethylphosphoryl)-N-(ethyl)-N-(2-phenyl-2-hydroxyethyl) thiourea analyzing as 8.8% P ascompared to 8.6% P theoretical.

' To a solution of 18.2 grams (0.10 mole) of0,0-dimethylphosphoroisothiocyanato thionate in 100 ml. of benzene wasadded a solution of 8.9 grams (0.10 mole) of N-ethyl ethanolamine over aminute period at room temperature. The reaction mixture was allowed towarm to 35 C. during the addition and was stirred for an additional hourafter the addition was complete. After removing the solvent'underpartial pressure the product was concentrated to 50 C. at 1.0 mm. of Hgpressure to yield 27.0 grams (93% of theoretical yield) of N-(0,0-dimethylphosphorothiono) N (ethyl)-N'-(,8-hydroxy-' ethyl) thioureaanalyzing as 11.2% P and 22.5% S, as" compared to 11.4% P and 22.8% Stheoretical.

Example 5 To a solution of 35.9 grams (0.15 mole) ofdiisopropylphosphoroisothiocyanato tbionate in ml. of hen- Zene Wasadded 9.2 grams (0.15 mole) of ethanolamine at 15 C. over a 20 minuteperiod. The product separated as an oil which Was washed with benzeneand hexane and then concentrated to 50 C. at 1.0 mm. of Hg pressure toyield 24.5 grams (65% of theoretical yield) of N-(0,0diisopropylphosphorothiono)-N-(fi-hydroxyethyl) thiourea, analyzing as10.4% P and 21.5% S, as compared to 10.3% P and 21.3% S theoretical.

Using a procedure substantially in accordance with one or more of thosedescribed in the foregoing examples, the following specific compoundswere prepared.

N-(0,0-diethylph0sphoryl) N (ethyl) N (fi-hydroxyethyl) thiourea;percent yield=97.0%; found: 10.8% P and 11.1% S; theory: 10.9% P and11.3% S.

Example 7 (C H O) P S) NHC (S )-NHCH CH O N-(0,0 diethylphosphorothiono)N (Q-hydroxyethyl) thiourea; percent yield=87.0; found: 11.2% P and22.8% S; theory: 11.0% P and 23.4% S.

Example 8 I (C H O P O 'NHC (S)NHCH CH OHN-(0,0-diethylphosphoryl)-N'-(B hydroxyethyl) thiourea; percentyield=82.0; found: 11.7% P and 12.0% S; theory: 12.1% P and 12.5% S.

N (0,0 dimethylphosphorothiono)-N,N-di-(fi-hydroxyethyl) thiourea; N=1.5398; percent yield: 86.0; found: 10.5% P and 22.5% S; theory: 10.7%P and 22.2% S.

Example 11 N (0,0 dimethylphosphorothiono)-N'-(hydroxyethyl) thiourea;percent yield=94.0; found: 12.5% P and 24.7% S; theory: 12.7% P and25.2% S.

Example 12 2 5 )2 3) z l N (0,0 diethylphosphoryl) N(methyl)-N-l1ydroxyethyl) thiourea; N =1.5045; percent yield=97.0;found? 11.3% P and 12.1% S; theory: 11.5% P and 11.9% S.

Example 13 z s )2 s) Z a N-(0,0 diethylphosphorothiono) N (methyl)-N-(hydroxyethyl) thiourea; percent yield=9l.0; found: 10.9% P and 20.7% S;theory: 10.9% P and 22.4% S.

Example 14 (CH O) P (S)NHC(S)N(CH (C H OH) N (0,0dimethylphosphorothiono) N (methyl)- N' (hydroxyethyl) thiourea; N:1.5541; percent yie1d=97.5; found: 10.8% P and 24.3% S; theory: 12.0% Pand 24.8% S.

Example z 5 )z 3 T 2 4 N-(0,0-diethylphosphoryl) N(isopropyl)-N'-(hydroxyethyl) thiourea; N =1.5055; percent yield==92.5;found: 10.2% P and 9.9% S; theory: 10.4% P and 10.7% S.

Example 16 a )2 a T (C2H4OH) N-(0,0-dimethylphosphorothiono) N(isopropyl)- N (hydroxyethyl) thiourea; N =l.5439; percent yield=91.0;found: 10.2% P and 21.3% S; theory: 10.7% P and 22.0% S.

Example 17 N-(0,0 dimethylphosphorothiono) N' (octyl)-N'- (hydroxyethyl)thiourea; percent yield=82.3; found: 8.8% P and 16.1% S; theory: 8.8% Pand 17.9% S.

N-(0,0 diethylphosphoryl)-N-(octyl)-N-(hydroxymethyl) thiourea; N=1.473l; percent yield=94.6; found: 8.9% P and 7.7% S; theory: 8.5% Pand 8.7% S.

Example 19 N 0,0 diethylphosphoryl) N (phenyl)-N-(h droxyethyl)thiourea; N =1.5647; percent yield=97.0; found: 10.4% P; theory: 10.7%P.

Example 20 2 5 )2 B 5)( 2 4 N-(0,0 diethylphosphorothiono) N(phenyl)-N'- (hydroxyethyl) thiourea; percent yield=97.5; found: 9.0% Pand 16.1% S; theory: 8.9% P and 18.3% S.

N (0,0 dirnethylphosphorothiono) -N-(phenyl)-N'- (hydroxyethyl)thiourea; percent yield=98.0; found: 10.3% P and 18.6% S; theory: 9.7% Pand 19.9% S.

Example 22 N (0,0 dimethylphosphorothiono) N(p-chlorophenyl)-N-(hydroxyethyl) thiourea; percent yield=97.6; found:8.7% P and 16.9% S; theory: 8.9% P and 18.2% S.

Example 23 N-(0,0-diethylphosphoryl) N (hydroXyethy1)-N'-(p-methoxyphenyl) thiourea; percent yie1d=91.0; found: 8.2% P and 8.2%S; theory: 8.2% P and 8.4% S.

Example 25 N-(0,0 diethylphosphoryl) N' (hydroxyethyl)-N'-(p-chlorophenyl) thiourea; percent yield=89.0; found: 8.3% P and 8.1% S;theory: 8.4% P and 8.6% S.

6 Example 26 N- (0,0diethylphosphorothiono)-N-(p-chloropheny1)-N'-(hydroxyethyl) thiourea;percent yield=96.0; found: 8.1% P and 15.9% S; theory: 8.2% P and 16.7%S.

Example 27 N.-(0,0-diethy1p11osphorothiono) N(hydroxyethy1)-N-(p-rrnethoxyphenyl) thiourea; percent yie1d=94.0;found: 8.1% P and 16.7% S; theory: 8.2% P and 16.9% S.

N-(O,O'-diethyllphospl1orothiono) N (octy1)-N- (hydroxyethyl) thiourea;pencent yield=94.0; found: 8.1% P and 15.1% S; theory: 8.2% P and 16.6%S.

Example 29 (C H O) P O) NHO(S) N( C H (CH CHOHCHN(0,0-diethylphosphoryl)-N-(ethyl) N (2-hydroxypropyhl) thiourea;percent yield=97.4; found: 10.6% P and 9.7% S; theory: 10.4% P and 10.7%S.

Example 30 (C H O P (S NHC(S) N(C H (CH CHOHCHN-(0,0-diethylphosphorothiono) N (ethyl) -N'- (2- hydroxypropyl- 1)thriourea; penoent yield=94.5; found: 8.9% P and 18.4% S; theory: 9.8% Pand 20.2% S.

Example 31 N-(0,0-dimethylphosphorothiono) N (ethy1)-N-(Z-hydroxypropyal-l) thiourea; percent yield=100.0; found: 10.5% P and22.1% S; theory: 10.8% P and 22.3% S.

Example 32 (C H O) P(S)NHC(S)--N(CH (CH CHOHCHN-(0,0-diethylphosphorothiono) N (methyl)-N- (2-hydroxypropyl- 1)thiounea; pecncent yie1d=98.5; found: 10.4% P and 20.4% S; theory: 10.3%P and 21.2% S.

Example 33 N-(O,Q-diethylphosphorothiono) -N'-(ethyl) N (2-hydroxy-Lphenyl ethyl) thiourea; percent yield: 100.0;

found: 8.1% P and 16.9% S; theory: 8.2% P and 17.0% S.

found: 9.5% P and 17.9% S; theory: 8.9% P and 18.3% S.

Examp 5 30)2 )NH 3) (CHZCHOHCHS) N-.(0,0-djmkethylphosphorothiono). N'(methyl) N- (2-Jhyd1roxypropy1- 1) thiourea; percent yield=97.6; found:11.6% P and 22.6% S; theory: 11.4% P and 23.5% S.

Example 36 Example 37 N-(0,0-diethylphosphoryl)-N'-.(methyl) N(Z-hydroxybutyl-l) '4 thiourea; percent yield=98.5; found: 10.8% P and10.5% S; theory: 10.31% P and 10.6% S.

Insecticidal activity for the compounds of the fore going examples isillustrated in Table 11 wherein the percentage kill among the pestspecies is reported for a specified quantity of candidate compoundexpressed in micrograms (herein termed the bioassay test) or for apercentage concentration of the compound in aqueous dispersion (hereintermed the screening test). A slanted line is used to separate thepercentage kill from the test species shown on the left and thepercentage concentration or total quantity, shown on the right.

TABLE II Mortality of Representative Species of Common Insec Orders Inthe screening tests for the insect species of Table II, from ten totwenty-five insects were caged in cardboard mailing tubes 3%" indiameter and 2%" tall. The cages were supplied With cellophane bottomisand screen tops. Food and water were supplied to each cage. Dispersionsof the test compounds were prepared by dissolving one half gram of thetoxic material in ml. of ace tone. This solution was then diluted withwater containing 0.015% Vatsol (a sulfonate-type wetting agent) and0.005% Methocel (methyl cellulose) as emulsifiers, the amount of Waterbeing sufficient to dilute the active ingredients to a concentration of0.1% or below. The test insects were then sprayed with this dispersion.After twenty-four and seventy-two hours, counts were madeto determineliving and dead insects.

Some of the compounds which showed high mortality on house flies in thescreening test were bioassayed on M. domestica. toxicant was placed in aconfined area. The same cages were employed as for the fly screeningtest. A weighed amount of the toxicant was placed in a 60 mm. diameterPetri dish along with 1 ml. of acetone containing light spray oil. Afterthe solution air-dried, a cage containing twenty-five female 'fiies wasplaced over the residue. Counts of living and dead insects were madeafter twentyfour and seventy-two hours.

It has been further found that the compounds of the present inventionare excellent systemic miticides. In testing for systemic action, pintobean plants were placed in bottles containing 200 m1. of the testsolution and were held in place with cotton plugs. were immersed. Thesolutions were prepared by dissolving the candidate miticide in acetoneor other suitable solvent and then diluting with distilled Water.The'final acetone concentration. of the solution was never allowed Inthis test, a known quantity of they ditions of use.

to exceed 1% and the toxicant was initially tested at a concentration of100 plpzm'. As soon as the plants were placed in the solution they wereinfested with mites. Mortalities of both embryonic and post-embryonicforms were determined fourteen days after initiation of the test. Bythis test, post-embryonic mortalities of 100% have been found atconcentrations of 10 ppm of the test compound, for the compounds ofExamples 10, 14, and 16 shown above. Embryonic mortality has been alsodetermined to be rather high.

Although the above tests were accomplished with aqueous dispersions, thetoxic compounds can also be used commercially in the form of aqueoussolutions, when appreciably solublenon-aqueous solutions, wettablepowders, vapors, and dusts as best suited to the con- In manyapplications fillers will be incorporated with the toxic compounds. Formore specialized application, the material may even be used in its pure,undiluted form.

Where used herein the term pest" is intended in the restricted sensegenerally recognized in the art as apply ing to the lower forms of lifecustomarily controlled by chemical means and excluding the higheranimals, the vertebrates, for example, rodents, birds, and larger formswhich are more commonly controlled by mechanical means such as traps. Itwill be apparent to one skilled in the art that the toxic activitydemonstrated hereinbefore on various test species is indicative ofactivity with species and orders not specifically shown.

The foregoing description is given for clearness of understanding onlyand no unnecessary limitations should Qnly the roots be understoodtherefrom, as modifications will be obvious to those skilled in the art.

We claim:

1. A compound having the formula:

wherein R and R are lower-alkyl, X is selected from the group consistingof sulfur and oxygen, R is selected from the group consisting of lowerhydroxyalkyl and phenylsubstituted lower hydroxyalkyl radicals, and R isselected from the group consisting of hydrogen, loWer-alkyl, aryl, and Ras previously defined.

2. N (0,0 diethylphosphorothiono) N (phenyl)- N'-(hydroxyethyl)thiourea.

3. N-(0,0-dirnethylphosphorothiono)-N'-(octyl) N- (hydroxyethyl)thiourea.

4. N-(0,0-dimethylphosphorothiono) N (ethyl-N- (B-hydroxyethyl)thiourea.

5. N-(0,0-dimethylphosphorothiono) N,N-di(fi-hydroxyethyl) thiourea.

6. A method of controlling pests which comprises contacting said pestswith a pesticidal amount of at least one compound having the formula:

wherein R and R are loWer-alkyl, X is selected from the group consistingof sulfur and oxygen, R is selected from the group consisting of lowerhydroxyalkyl and phenylsubstituted lower hydroxyalkyl radicals, and IRis selected from the group consisting of hydrogen, lower-alkyl, aryl,and R as previously defined.

7. A method of controlling posts which comprises contacting said pestswith a pesticidal amount of N-(0,0-dimethylphosphorothiono) N (ethyl) N(fl-hydroxyethyl) thiourea.

J 8. A method of controlling pests which comprises contacting said pestswith a pesticidal amount of N-(0,0-di- 3,083,135 9 10methylphosphorothiono)-N-(methyl) N' (,S-hydroxy- References Citedin thefile of this patent ethyl) thiourea. 0 PA NT 9. A method of controllingpests which comprises con- F REIGN TE S tacting said pests with apesticidal amount of N-(0,0-di 952,712 Germany 1956 ntlgllgliakllgsuprlgrothiono)-N'-(isopropyl-N'-(B hydroxy- 5 OTHER REFERENCES 6 1 i6n 10. A method of controlling pests which comprises con- 1 gglchalskl atall Roczmkl Chem" VOL 1957 tacting said pests with a pesticidal amountof N-(0,0-di- D methylphosphomthiono) (octyl) (fi hydroxy Levchenko etal.. Zhurnal Obsche. Khlmn, vol.

ethyl) thiourea 1O 29, N0. 4, 1959, pp. 1249-1254.

1. A COMPOUND HAVING THE FORMULA: